The antiemetic interaction of Δ9-tetrahydrocannabinol when combined with tropisetron or dexamethasone in the least shrew

5-HT3 receptor antagonists (e.g. tropisetron) combined with dexamethasone are effective for the acute phase of cisplatin (CIS)-induced emesis. This study determined the possible additive or synergistic antiemetic efficacy of Δ9-THC when combined with tropisetron or dexamethasone (DEX). Δ9-THC (0–10 mg/kg i.p.) was injected in combination with tropisetron (0–5 mg/kg i.p.) or dexamethasone (0–20 mg/kg i.p.) prior to CIS (20 mg/kg i.p.) in the least shrew, and the induced emesis was recorded for 60 min. CIS-induced vomiting was dose-dependently and significantly attenuated by individual administration of Δ9-THC (59–97% reductions) and tropisetron (79–100% attenuation), but not dexamethasone (26–40%), although a trend (p < 0.1) towards reduced vomiting frequency following DEX was noted. Low doses of Δ9-THC (0.25 or 0.5 mg/kg) when combined with low doses of tropisetron (0.025, 0.1, or 0.25 mg/kg) were more efficacious in reducing emesis frequency than when given individually, but Δ9-THC had no antiemetic interactions with DEX. However, no tested combination provided a significantly greater effect on the number of animals vomiting than their individually-administered counterparts. The modest interaction of Δ9-THC with tropisetron suggests they activate overlapping antiemetic mechanisms, while the lack of interaction with dexamethasone needs further clarification.